The effect of basal insulin glargine on the fibrinolytic system and von Willebrand factor in people with dysglycaemia and high risk for cardiovascular events: Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial.

INTRODUCTION: Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization with insulin glargine might improve the levels of these factors. METHODS: Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years). RESULTS: Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in the insulin glargine but not in the standard care group. CONCLUSION: In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments.

Markers of fibrinolysis may predict development of lower extremity arterial disease in patients with diabetes: A longitudinal prospective cohort study with 10 years of follow-up.

BACKGROUND: A previous cross-sectional study suggested that tissue plasminogen activator-activity might be an early marker of asymptomatic lower extremity arterial disease, but the long-term relationship is unknown. SUBJECTS AND METHODS: This study included 96 diabetic (48 type 1/48 type 2) and 62 non-diabetic subjects aged 30-70 years without previously known lower extremity arterial disease (age: 50.3 ± 9.3 years, gender: M/W 47.5/52.5% and body mass index: 26.6 ± 4.5 kg/m(2)). The relationships between asymptomatic lower extremity arterial disease and fibrinolytic markers (tissue plasminogen activator-activity, tissue plasminogen activator-mass, plasminogen activator inhibitor-1 activity) at baseline and after 10 years were assessed by logistic regression analysis adjusting for age, hypertension, statin treatment, HbA1c, triglycerides and low-density lipoprotein cholesterol as fixed covariates. RESULTS: The tissue plasminogen activator-activity at baseline and at the 10-year follow-up significantly predicted the presence of sign(s) of lower extremity arterial disease (odds ratio = 1.78, 95% confidence interval: 1.02-3.10, p = 0.043 and odds ratio = 1.78, 95% confidence interval: 1.12-2.23, p = 0.014, respectively). In addition, tissue plasminogen activator-mass at the 10-year follow-up was associated with signs of lower extremity arterial disease (odds ratio = 1.07, 95% confidence interval: 1.00-1.15, p = 0.046). Baseline age, hypertension and HbA1c were independently associated with sign(s) of lower extremity arterial disease at 10 years (odds ratio = 1.09, 95% confidence interval: 1.04-1.14, p = < 0.001; odds ratio = 3.68, 95% confidence interval: 1.67-8.12, p = 0.001 and odds ratio = 1.54, 95% confidence interval: 1.21-1.95, p = < 0.001, respectively). CONCLUSION: This long-term study supports previous findings of a significant association between asymptomatic lower extremity arterial disease and tissue plasminogen activator-activity. Thus, tissue plasminogen activator-activity may be an early marker of lower extremity arterial disease although the mechanism of this relationship remains unclear.

Favorable trends in the incidence and outcome in stroke in nondiabetic and diabetic subjects: findings from the Northern Sweden MONICA Stroke Registry in 1985 to 2003.

BACKGROUND AND PURPOSE: Several studies indicate a declining case-fatality and mortality in stroke. Little is known about time trends in stroke for subjects with diabetes. The purpose of this study was to compare time trends in incidence, case-fatality and mortality for stroke patients with or without diabetes. METHODS: This study was based on the Northern Sweden MONICA Project Stroke registry during 1985 to 2003. 15 382 patients, aged 35 to 74 years, were included in the study. 11 605 had a first-ever stroke and 3777 had a recurrent stroke. In both men and women previously diagnosed diabetes was found in 22.8%. RESULTS: The incidence of stroke was 5 and 8 times higher in diabetic subjects than in nondiabetics, in men and women, respectively. Incidence of first-ever stroke decreased for nondiabetic men, probability value <0.001, and for diabetic women, probability value=0.012. Recurrent stroke incidence declined highly significant, probability value <0.001, in all but diabetic men. For diabetic women, the decrease in incidence in first and recurrent stroke was significantly greater than in nondiabetic women. Case-fatality and mortality in stroke declined for all groups except diabetic women with first-ever stroke. The time trends in case fatality and mortality did not differ significantly between nondiabetic and diabetic patients. CONCLUSIONS: The incidence of stroke declined in both nondiabetic and diabetic subjects except for diabetic men and for nondiabetic women with first-ever stroke. Case-fatality in first-ever stroke declined for all but diabetic women. This led to a decreased mortality over the 19-year period for both groups. This is the first time that the decline in stroke incidence is reported in this MONICA population.